Process of coupling aldehydes and ketones

ABSTRACT

A process for producing coupling products from aldehydes and ketones by treating such compounds with manganese dioxide or nickel peroxide.

United States Patent 1 3,609,193

[72] inventor John Charles Leffingwell [51] Int. Cl ..C07c 49/76, Winston-Salem, N.C. C07c 49/26, C010 49/ l 2 [21] App]. No. 820,629 [50] Field of Search 260/590, [22] Filed Apr. 30, 1969 593,601,602, 599,598,600 R,586 R,5l4 R, 289 [45] Patented Sept. 28,1971 R, 326.16, 345.9, 297 R, 332.3 R, 347.8 [73] Assignee R. J. Reynolds Tobacco Company wi m s NC. [56] References Cited Continuation-impart of application Ser. No. UNITED STATES PATENTS now abandoned 2,751,406 6/1956 lpatieff et a1 260/590 FOREIGN PATENTS [54] PROCESS OF COUPLING ALDEHYDES AND 895,088 1/1945 France 260/586 KET9NES Primary Examiner-Daniel D. Horwitz 8 Claims, No Drawings Att0rney--Pendleton, Neuman, Williams & Anderson [52] US. Cl 260/590, 260/281, 260/289 R, 260/297 R, 260/326. 16, 260/332.3, 260/340.9, 26013459, 260/343.3, 260/347.8, 260/465.8 R, 260/472, 260/514 R, ABSTRACT: A process for producing coupling products from 260/515 P, 260/586 R, 260/598, 260/599, aldehydes and ketones by treating such compounds with man- 260/593, 260/600, 260/601, 260/602 ganese dioxide or nickel peroxide.

PROCESS OF COUPLING ALDEHYDES AND KETONES This application is a continuation-in-part of my prior copending application Ser. No. 595,004 filed Nov. 17, l966.

This invention relates to synthesis of organic compounds and more particularly to the synthesis of organic compounds from aldehydes an ketones.

In general, the present invention relates to the discovery that manganese dioxide and nickel peroxide can be employed advantageously to treat aldehydes and ketones to form therefrom coupling products. The synthesis is applicable generally to the conversion of aldehydes and ketones having at least one hydrogen atom in alpha position to the carbonyl function.

The conversion of aldehydes in accordance with the synthe sis of this invention can be generally illustrated as follows:

Rqlkyl of one to 10 carbon atoms, cycloalkyl of from three to eight carbon atoms, alkenyl of from three to 10 carbon atoms, aryl of from six to 10 carbon atoms, heterocyclic of from four to nine carbon atoms, aralkyl of from seven to ll carbon atoms,

R: alkyl of one to 10 carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of from three to l carbon atoms, aryl of six carbon atoms, heterocyclic of four or five carbon atoms, and

CH RI considered as a unit is an cycloalkyl radical of three to eight carbon atoms, and each of the said hydrocarbon groups can be with or without additional substituents such as halogen, alkoxy, nitro and the like.

Similarly, the conversion of ketones can be generally illustrated as follows:

R=alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of four. to six carbon atoms, aryl of six to carbon atoms, heterocyclic of four to nine carbon atoms, aralkyl of eight to 13 carbon atoms, and alkaryl of seven to 11 carbon atoms,

R'= alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, aryl of six carbon atoms, heterocyclic of four or five carbon atoms and alkaryl of seven carbon atoms, and

considered as a unit is an cycloalkyl radical of three to eight carbon atoms,

R"=alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of two to eight carbon atoms, aryl of six to 10 carbon atoms, heterocyclic of four to eight carbon atoms, aralkyl of eight to 14 carbon atoms and alkaryl of seven to 11 carbon atoms, and each of the said hydrocarbon radicals can be with or without additional substituents such as halogen, alkoxy and the like.

Representative groups for R and R thus include phenyl, pmethoxyphenyl, 4-t-butylphenyl 4-hexylphenyl, 4-phenylhexyl, 4-hexenyl, pyridyl, thienyl, furyl, p-chlorophenyl, pnitrophenyl, m-methoxyphenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, propyl, isopropyl, butyl, pentyl, isobutyl, and the like; R and R being the same or different Representative groups for R" thus include phenyl, p-methoxyphenyl, p-chlorophenyl, p-nitrophenyl, m-methoxyphenyl, pyridyl, thienyl, furyl, eyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methyl, ethyl, propyl, butyl, isobutyl, pentyl, 4-hexenyl, 4-phenylhexyl and the like. Specific examples of aldehydes and ketones which can be treated in accordance with the invention are 2ethylbutyruldehyde, 2- ethylhexanal, 2-ethyl-3-methylbutyraldehyde. isobutyraldehyde, 2-methylbutraldehyde, Z-methylundeeanal, 2- isopropyl-3-methylbutyraldehyde, 2,3-dimcthylbutyraldehyde, 2-decyldodecanul, a-methylcyclopentane-acetaldehyde, a-methylcyclohexaneacetaldehyde, a-methyleyclopropaneacetaldehyde, 2,2-dicyelopropylacetaldehyde, a-methyl-eyelobutaneacetaldehyde, a-methylcycloheptaneacetaldehyde, a-methyleyclooctaneacetaldehyde, 2,2- dieyclohexylacetaldehyde, 2,Z-dicyclopentylacetaldehyde, 2- cyclopropyl-Z-phenylacetaldehyde, a-phenylcyclohexaneacetaldehyde, a,3-dimethylcyclohexane-acetaldehyde, 2- methyl--heptcnal, 2-ethyl-6-heptenal, 2-phenyl-6-heptenal, 2-methyl-6-octenal, Z-decenyldodeeenal, cyclopentanecarboxaldehyde, cyclohexanecarboxaldehyde, Z-norbornanecar boxaldehyde, 5-norbornene-Z-carboxaldehyde, cyclopropanecarboxaldehydc, cyclobutanecarboxaldehyde, cycloheptanecarboxaldehyde, cyclooctaneearboxaldehyde, octahydto-indanecarboxaldehyde, pmenthane7-carboxaldehyde, 2,Z-diphenylacetaldehyde, Z-phenyl-propionaldehyde, Z-p-ainsyl)-propionaldehyde 2-(4-chlorophenyl)- propionaldehyde, 2,2-di-p-anisyl-acetaldehyde Z-phenyl-butyraldehyde, 2-( l'-napthyl)-propionaldehyde, 2-( l -napthyl)- 3-methylbutyraldehyde, 2-(2'2'-furyl)-propionaldehyde, 2,2- di-(2-furyl)-acetaldehyde, 2-(2'-furyl)-hexanal, 2-(2'-furyl)- 3-methylbutyraldehyde, 2-(2-pyrryl)-propionaldehyde, 2,2- di-(2-pyrryl)-acetaldehyde, 2-(2'-pyrryl)-3-methylbutyraldehyde, 2-(2-thienyl)-propionaldehyde, 2,2-di-(2'-thienyl)- propionaldehyde, 2-(2-thienyl)-3-methylbutyraldehyde, 2- (3 '-pyridyl )-pr0pionaldehyde, 2,2-di-( 3 '-pyridyl )-acetaldehyde, 2-(3-pyridyl)-3-methylbutyraldehyde, 2-(3-indolyl )-propionaldehyde, 2-( 3 '-indolyl )-3-methylbutyraldehyde, 2-(4'-quinolyl)-propionaldehyde, 2-(4-quinolyl)-3- methylbutyraldehyde, 2-(4'-amlphenyl)-propionaldchyde, 2- (2'-methylphenyl)-propionaldehyde, 2-(4'-methylphenyl)- propionaldehyde, 2-(4'-methylphenyl)-butyra|dehyde, 2,2-di- (4'-amylphcnyl)-acetaldehyde, 2-methyl-5-phenyl hexanal, 2- ethyl-5-phenyl hexanal, 2-methyl-5-phenyl pentanal, Z-ethyl- 4-phenyl butyraldehyde, 2,4-dimethyl-3-heptanone, 3,5- dimethyl-4-heptanone, 2,4-dimethyl-3-hexanone, 2,4- dimethyl-3-pentanone, 2-methyl-3-heptanone, 3-methyl-2- heptanonc, 4-methyl-3-heptanone, 2-methyl-3-hexanone, 3 methyl-2-hexanone, 3-methyl-4-nonanone, 3-methyl-4-oc tanone, 2-methyl-3-pentanone, 2-methyl-3-butanone, 3- methyl-Z-decanone, cyclopentyl methyl ketone, cyclohexyl methyl ketone, 3-isopropylcyclopentyl methyl ketone, 3- 5 methylcyclopentyl isopropyl ketone, cyclopropyl methyl ketone, cyclobutyl methyl ketone, cyclohexyl butyl ketone, cycloheptyl methyl ketone, cyclooctyl methyl ketone, cyclopropyl phenyl ketone, cyclopentyl phenyl ketone, cyclopropyl p-totyl ketone, 2-phenyl-l,3-indane-dione, cyclobutyl phenyl ketone, cyclohexyl phenyl ketone, cyclopropyl 4-methoxyphenyl ketone, cyclopropyl 4- fluorophenyl ketone, cyclobutyl 4-fluorophenyl ketone, pinonic acid, 2-methyl-5-cyclopropyl-3-pentanone, Z-methyl- S-cyclobutyl-3-pentanone, 2-methyl-4-cyclohexyl-3-butanone, 2-methyl-4-cyclopentyl-3-butanone, 2-cyclohexyl-3- butanone, dicyclohexyl ketone, Z-cyclopropyl-3-butanone, 2- methycyclopentanone, 2-methylcyclohexanone, 2-phcnylcyclohexanone, 2-(3-pyridyl)-cyclohexanone, Z-phenyl- 20 cyclopentanone, carvementhone (pmethan-2-one), 2- methylcycloctanone, l-methyl-Z-decalone, 3-methyl-2-decalone, 2-methyl-7-octen-3-one, 3-methyl-6-hepten-2-one, 3- methyl-7-octen-2-one, Z-methyl-S-nonen-El-one, 2-methyl-4- penten-3-one, 4-methyl-l-hexen-3-one, 2-methyl-4-decen-3- one, cyclopentyl vinyl ketone, cyclopropyl vinyl ketone, cyclohexyl vinyl ketone, isoamyl vinyl ketone, Z-methyl-S- phenyl-4-penten-3-one, 2-methyl-5(p-anisyl)-4-penten-3-one, 2-methyl-5-(C4'-chlorophenyl)-4-penten-3-one, 2-methyl-5-(4 "methylphenyl)-4-penten-3-one, 3-(p-anisyl)-4-hexanone, l- (3 ,4-dimethoxyphenyl )-acctone, l-( 3 ,4 '-dimethoxyphenol- 2-butanone, 1,1-diphenylacetone, 1,3-diphenylacetone, phenylacetone, l-phenyl-Z-butanone, p-anisyl benzyl ketone, isobutyrophenone, l-napthylacetone, Z-furyl isopropyl ketone, Z-furyl-methylpropyl ketone, 2-(2-fruyl)-3-butanone, 2-(2-furyl)-3-pentanone, 2-pyrryl isopropyl ketone, 2-(2'- pyrryl)-3-butanone, 2-thienyl cyclopropyl ketone, 2(2-thienyl)-3-butanone, 2 thienyl isopropyl ketone, 2-pyridyl isopropyl ketone, l-(2'-pyridyl)-acetone, 3-indolyl isopropyl ketone, l-(3-indolyl)-acetone, l-(l '-napthyl)-acetone, 1-(4'- quinolyl)-acetone, 4-quinolyl isopropyl ketone, l,l-di-(2'- pyridyl)-acetone, l,l-di-(2-furyl)-acetone, p-tolyl isopropyl ketone, 4-amylphenyl isopropyl ketone, 4-amylphenyl isopropyl ketone, 2-(p-tolyl)-3-butanone, 2-(4amylphenyl)-3 -butanone, l-(p-tolyl)-acetone, 1,1-di-(p-tolyl)-acetone, 3- methyl- 5-phenyl-2-pentanone, 2methyl-6-phenyl-3undecanone, 2-methyl-6-(p-anisyl)-3-undecanone and l-phenyl- 3-methyl-4-octanone.

The syntheses of this invention are carried out by contacting an aldehyde or ketone with manganese dioxide or nickel peroxide for a period sufficient to permit the desired reaction to proceed. Contacting of the aldehyde or ketone with the specified metal oxides can be accomplished in any convenient manner. For example, an aldehyde or ketone can be slurried with the specified metal oxides in a solution of an inert solvent. The reaction can be carried out at temperatures ranging from about ambient to 200 C. and preferably at a temperature ranging from 70 to 180 C. for a period of time to permit the reaction to proceed, which may range from one half to 200 hours. The reaction is preferably conducted in an inert atmosphere particularly in the case of aldehydes to prevent air oxidation to acids. An inert solvent such as hexane, dioxane, pentane, tetrahydrofuran, benzene, pyridine, tertiary butanol, methylene chloride chloroform and the like can be employed. Another alternative procedure for conducting the reaction is to pass the aldehyde or ketone through a bed of the specified metal oxide. Preferably the aldehyde or ketone is passed through the metal oxide bed as a solution in an inert solvent. 70 Repeated passes of the aldehyde or ketone through the metal oxide bed can be carried out to insure high conversion. It is preferred that the unreacted aldehyde or ketone be recycled through the reactor bed until a conversion of at least 40 to 90 percent has been achieved.

Essentially the same reaction conditions can be employed for the conversion of both aldehydes and ketones; ketones, however, react at a slower kinetic rate and therefore in some cases it may be desirable to employ longer reaction periods and higher temperatures with ketones.

At the end of the reaction period the metal oxides can be separated by filtration (in the case of a slurry procedure) and the solvent and unreacted starting materials removed by distillation, crystallization, chromatography or by other means. The resultant products may be separated by distillation, liquid phase chromatography or gas phase chromatography or a combination of such methods.

The nickel peroxide or manganese dioxide is employed in the synthesis of the invention in amounts ranging from about 1.5 to 10 moles per mole of the starting aldehyde or ketone. Anhydrous or hydrated manganese dioxide ores commonly used in organic synthesis can be employed, although it is usually preferred to use activated manganese dioxide prepared by modifications of the Attenburrow Procedure as described in Journal afC/zemical Society, i952, 1094-] l l l (p. l l04). Preferably the nickel peroxide employed is prepared as described in Journal of Organic Chemistry, 27, 1592-1601 1962) although other nickel peroxides can be employed.

The following specific examples illustrate the synthesis of this invention.

EXAMPLE I Reaction of lsobutyraldehyde with Manganese Dioxide A mixture of 14 grams isobutyraldehyde, 30 grams activated manganese dioxide and milliliters dioxane was refluxed (approximately 100 C.) for 24 hours in a round bottom flask equipped with stirrer and reflux condenser. An inert atmosphere of nitrogen under a very slight positive pressure was maintained over the reflux mixture by means of a balloon connected to a gas inlet-outlet valve attached to the condenser outlet. At the end of the reaction period the vessel was cooled and the manganese oxide was removed by filtration. Vaporphase chromatographic analysis over a 20 percent C arbowax on Chromosorb W (60-80 mesh) column indicated two major product peaks in a ratio of about 1:1 The solvent and unreacted starting material were removed by distillation to give a thick viscous material which on further distillation gave approximately 4.l grams of material boiling point l30-l98 arbitrarily taken in four fractions, approximately 4.5 grams of residue were left in the distillation flask which afforded 0.8 gram of white crystalline material on sublimation. Vapor-phase chromatographic analysis of the combined distilled and sublimed material indicated four products, the first two of which were the same as those observed in the vapor-phase chromatography of analysis of the crude product before distillation. The four products (A, B, C and D) were identified as follows in order of their elution off the chromatographic column described above; purification of the individual products was by vapor-phase chromatography.

Product B was identified as 2-methyl2-(2-methyl-l propenoxy)-propionaldehyde by virtue of its extremely characteristic spectra; the infrared spectrum afforded bands at 3.66 ,u. (weak) and 5.75 (strong) corresponding to a saturated aliphatic aldehyde (-CH=O) and a band at 5.93 n of moderate intensity corresponding to the olefinic absorption of the vinyl ether linkage while the ether absorption appeared at 8.75 p. (very strong); the nuclear magnetic resonance spectrum exhibited a gem dimethyl absorption at 8.75 1', allylic methyls centered at 8.75 7, an olefinic proton at 4.34 -r and the aldehydic proton at 0.55 -r; the nuclear magnetic resonance proton integration was correct for the above structural assignment; the mass spectrum gave a molecular ion at mass m/e 142.

Product C was identified as tetramethylsuccinaldehyde from its spectral characteristics: the infrared spectrum showed absorptions at 3.59 p. and 5.76 a corresponding to the saturated aldehyde H=0) the nuclear magnetic resonance spectrum exhibited gem dimethyl absorption at 8.84 'r and aldehydic proton absorption at 0.53 r in ration of 6:1; the mass spectrum gave a molecular ion at m/e 142.

Product A was identified as 2-isopropyl-4,4-dimethyl-l,3 dioxolane by its spectral characteristics. Product peak D was identified as the y-lactone of 2,2,3,3-tetramethyl-4-hydrox ybutyric acid. Both Products A and D form during distillation.

EXAMPLE 2 A solution of 35 grams of isobutyraldehyde and 160 grams tetrahydrofuran were passed at reflux temperature (approximately 100 C.) through a bed of 25 grams of activated manganese dioxide (-20 mesh) in such a manner that the unreacted aldehyde was continuously recycled while the reaction products were concentrated in the reflux pot. The reaction is carried out so that the condensed solvent and aldehyde vapors are allowed to drip through a fiber cup (containing the manganese dioxide) back into the reflux pot.

After 105 hours of reflux and recycling, the solvent and unreacted isobutyraldehyde were removed by distillation leaving 23.5 grams of moderately viscous oil containing a small amount (0.1 g.) of a white crystalline material which was removed by filtration. Vapor-phase chromatographic analysis both before and after distillation indicated two major dimeric products which were identified as 2-methyl-2-(2'-methyl-1'- propenoxy)-propionaldehyde and tetramethylsuccinaldehyde by direct comparison with known samples. Distillation of a portion of this product mixture afforded material boiling point 5055 C. (7 mm.) which was essentially pure 2-methyl2-(2 '-methyl-1-propenoxy)-propionaldehyde and material 75- 83 (7 mm.) which soon solidified and was identified as predominantly tetramethyl-succinaldehyde; the product ratio being 5:4 respectively.

EXAMPLE 3 A run similar to example 2 employing 18 grams of isobutyraldehyde, 50 grams of manganese dioxide and 150 grams of tetrahydrofuran afforded after 48 hours 16.7 grams of a mixture which was identified as 50 percent 2-methyl-2-(2' methyl-1 -propenoxy)-propionaldehyde, 38 percent tetramethylsuccinaldehyde and 12 percent by-products. The reaction illustrated corresponds to the equation:

EXAMPLE 4 Reaction of 2-Methylbutyraldehyde with Manganese Dioxide A reflux mixture similar to that in example 1 was prepared except that 45 grams of Z-methylbutyraldehyde, 35 grams of activated manganese dioxide and 230 milliliters of dioxane were employed. After a reaction time of 48 hours, the manganese oxides were removed by filtration and the resultant solution cxhibited only two product peaks on vapor-phase chromatographic analysis, A and B, in a ratio of 3:2. The sample was stripped of solvent and unreacted starting material by distillation under reduced pressure and the two products separated by preparative vapor-phase chromatography.

Product A was identified as a mixture of cisand trans-2- methyl-2-(2'-methyl-l'-butenoxy)-butyraldehyde by the following spectral data: the infrared spectrum exhibited aldehyde (CH=O) absorptions at 3.70 p. and 5.74 a, olefin absorption at 5.95 p. and a strong band at 8.74 p, suggestive of the ether the nuclear magnetic spectrum confirmed the postulated structure, giving absorptions centered at 9.02 r 9.12 'r corresponding to CH CH groupings, singlet methyl absorption at 8.77 1- corresponding to the linkage, allylic methyl absorptions at 8.37 -r and 8.45 -r, olefinic proton absorption due to the protons at 4.15 r and aldehydric proton absorption at 0.35 r; from the doubling of many of the pertinent absorptions it was apparent that the sample was a 3:2 mixture of trans and cis isomers; the proton integration was consistent l'he mass spectrum of A gave a molecular ion peak at m/e 170 and M- (CHO) peak at m/e 141.

Product B was identified as a 1:1 mixture of mesoand d1- 2,3-diethyl-2,3-dimethylsuccinaldehyde from the following data: the infrared spectrum cxhibited absorptions at 3.70 p. and 4.80 p. corresponding to saturated aldehyde groups; the nuclear magnetic resonance spectrum exhibited absorptions for the CH CH groups centered at 9.24 'r. the R;,CCH groups showed up at 8.97 r, and the aldehydic protons absorbed at 0.42 T and 0.49 r; the doubling of the aldehydic proton absorption as well as other pertinent peaks was indicative of the presence of equal amounts of two (dl and meso) diastereoisomers; the nuclear magnetic resonance proton integration was correct for this structure; the mass spectrum exhibited a small molecular ion peak at m/e 170 as well as a large MCH O (M-29) peak at m/e 141.

EXAMPLE 5 In a run similar to example 4. using 22 grams of 2-methylbu tyraldehyde, 50 grams of manganese dioxide, 65 cubic centimeters tetrahydrofuran and cubic centimeters of dioxane a yield of 19.4 grams of crude dimer mixture was obtained which analyzed as a mixture of 54.6 percent 2-methyl-2-(2- methyl-l-butenoxy)-butyraldehyde (cis and trans), 43.3 percent 2,3-diethyl-2,3-dimethylsuccinaldehyde (dl and meso) and 2.1 percent other products by vapor-phase chromatography.

EXAMPLE 6 Reaction of 2-Methylbutyraldehyde with Nickel Peroxide A mixture similar to that in example 1 was prepared except that 20 grams of Z-methylbutyraldehyde, 15.0 grams of nickel peroxide and cubic centimeters of dioxane were employed. The reaction was stirred at room temperature for a period of 30 minutes prior to heating to reflux (approximately 100 C.); when the reaction temperature reached 95 the black color of the nickel peroxide slurry turned. to a light green color. The reaction was cooled and filtered to remove the nickel oxides. The solvent and unreacted starting aldehyde were removed by distillation under reduced pressure to give 2.93 grams of dimeric material which consisted of a mixture of 2-methyl-2-(2-methyl-1'-butenoxy)-butyraldehyde (cis and trans) and 2,3-diethyl-2,3-dirnethylsuccinaldehyde (di and meso) in ratio of approximately 2:1, respectively. Identification was made by separating the components by preparative vapor-phase chromatography and spectral comparison with known samples.

EXAMPLE 7 Reaction of Z-Ethylbutyraldehyde with Manganese Dioxide A reflux mixture similar to that described in example 2 was prepared except that 105 grams of 2-ethylbutyraldehyde, grams of manganese dioxide and 80 milliliters of dioxane were employed. After a reaction period of 48 hours, the solvent and excess 2-ethylbutyraldehyde were removed to give 27.5 grams of crude product which analyzed as 50 percent 2-ethyl-2-(2'- ethyl-l'-butenoxy)-butyraldehyde and 13 percent tetraethylsuccinaldehyde along with 37 percent of numerous minor components were isolated by preparative vapor-phase chromatography and identified by their characteristic spectral properties.

The spectral characteristics of 2-ethyl-2-(2'-ethyl-l -butenoxy)-butyraldehyde were as follows: the infrared spectrum exhibited absorptions at 3.68 p and 5.74 u characteristic of the aldehyde group (CH=O) an absorption at 5.96 p. was assigned as the olefinic absorption and the ether function absorbed 8.6-8.8 u; the nuclear magnetic resonance spectrum exhibited singlet aldehyde proton absorption (Q=O) at 0.40 1-; olefinic proton absorption at 4.18 7, two allylic methylene groups CHaCHC=C as a quartet centered at 7.90 1'; two saturated methylene groups (CH CH -C-) centered at 8.30 1' and four saturated methyl groups centered at 9.1 r; the proton integral was correct; the mass spectrum gave a molecular ion at m/e 198.

The tetraethylsuccinaldehyde exhibited infrared absorptions at 3.69 'r and 5.80 1- indicative of saturated aldehyde while the nuclear magnetic resonance spectrum exhibited a singlet aldehyde proton absorption at 0.25 1', quartet methylene absorptions (CH CH at 8.28 'r and triplet methyl absorptions (Ch Cl-l centered at 9.20 r.

A fraction isolated by preparative vapor-phase chromatography and comprising 3.8 percent of the total product mixture was identified as Z-ethylbutanol by infrared comparison of a known sample; also, 0.65 gram of material identified as the manganese salt of a carboxylic acid was isolated from the crude product mixture.

The 2-ethy1-2-(2-ethyl-l-butenoxy)-butyraldchyde was conveniently separable from the product mixture by distillation and boiled at 6973 (5 mm.) a total of 13.0 grams of relatively pure material was thus obtained from 27.5 grams of crude product mixture. The tetraethylsuccinaldehyde remained in the pot residue.

EXAMPLES In a run similar to example 7 using 24 grams of 2-ethylbutyraldehyde, 70 grams of pyridine, 70 cubic centimeters of dioxane and 50 grams of manganese dioxide with a reaction time of 48 hours a total of 21.5 grams of crude product mixture was obtained that analyzed as 85.6 percent 2-ethyl-2-(2- ethyl-l '-butenoxy)-butyraldehyde, 10.6 percent tetraethyl succinaldehyde and 3.8 percent other products by vaporphase chromatography.

EXAMPLE 9 Reaction of 3-Methyl-2-butanone with Manganese Dioxide A reflux mixture similar to that described in example 1 was prepared except that 20 grams of 3-methyl-2-butanone, 25 grams of activated manganese dioxide and milliliters of dioxane were employed. After a reaction period of 48 hours, solvent and unreacted starting ketone were removed by distillation under reduced pressure to give 3.2 grams of crude product mixture. Distillation of this sample over a short path distillation head gave 1.48 grams of material, boiling point 96-l08 (12 mm.) which was essentially -90 percent one component by vapor-phase chromatography analysis. Further purification of this major component can be effected by preparative vapor-phase chromatography. The infrared spectrum of a pure sample of this major product component indicated a saturated ketone carbonyl absorption at 5.84 t. The nuclear magnetic resonance spectrum showed only two singlet absorptions at 8.82 'r and 7.88 1- in a ratio of 2:1. The mass spectrum gave a molecular ion peak at m/e I70, an M-H O peak at m/e 152 and an M-ketone peak at m/e 128. From the spectral data the product was identified as 334,4- tetramethyl-2,5-hexanedione.

EXAMPLElO Reaction of phenyl-Z-propanonc with Manganese dioxide A mixture of phenyl-Z-propanone (13.4 g), dioxanc (110 cc.) and manganese dioxide (35 g.) was prepared and agitated at reflux (approximately C.) under an inert atmosphere of nitrogen for a period of 24 hours. The solution was filtered to separate the insoluble manganese oxides and the solvent (dioxane) removed under reduced pressure to give a yellow crystalline solid which afforded 8.4 grams of a light yellow crystalline material from ethanol, melting point 205. which was identified as 3,4-diphenylhexane-2,5-dione by its very characteristic spectra. The infrared spectrum exhibited bands at 3.45, 5.85, 6.24, 6.3l, 6.67, 6.87, 7.04, 7.26. 7.35, 8.84, 8.67, 9.31, 9.68, 10.36, 13.41 and 14.20 microns. The nuclear magnetic resonance spectrum exhibited the acetyl methyl group (COCH at 8.12 1', the

protons at 5.40 'r and the aromatic protons at 2.58 t; the spectrum integrated correctly for 3,4-diphenylhexane-2,5-dione. The mass spectrum afforded a molecular ion at m/e 266.

EXAMPLE 11 Reaction of 2-phenylcyclohexanone with Manganese dioxide A mixture of 2-phenylcyclohexanone (25 g), dioxane l 15 cc.) and manganese dioxide (35 g.) was prepared and agitated at reflux (approximately 100 C.) for a period of 48 hours under an inert atmosphere of nitrogen. The solution was filtered to separate the insoluble manganese oxides and stripped of solvent (dioxane) under reduced pressure to give a dark oil (20.1 g.) from which a total of 8.51 grams of crystalline material was obtained from an ethanol solution. The crystallization afforded the dl and meso isomers, melting point 186L- 188L and melting point l32L-l34L, in approximately equal amounts. The infrared spectra of these samples showed strong saturated ketone carbonyl absorption at 5.87 z. The nuclear magnetic resonance spectra showed an integral of 5 aromatic and 8 aliphatic protons. The mass spectrum exhibited peaks at m/e 174 (/M+l m/e 172 /Ml) as well as at 144 and 130. A molecular ion peak was present in the range m/e 346 15.

From the foregoing it will be evident that the present invention provides a novel and simple one-step method for converting aldehydes and ketones to dimeric reaction products. The dimeric aldehydes or ketones find wide utility. Thus, the 1,4- dialdehydes and 1,4-diketones are useful as intermediates for preparing various chemical compounds of known utility. For example, the 1,4-dialdehydes are convenient precursors in the preparation of the corresponding imides such as 2,2,3,3- tetramethylsuccinimide, 2,3-diethyl-2,3-dimethylsuccinimide and 2,2,3,3tetraethylsuccinimide which are known central nervous system stimulants. Thus, the 1,4-dialdehydes are readily converted to the corresponding dinitriles by the known procedures of converting to the aldoximes and dehydration with an acid chloride; such dinitriles can then be transformed in high yields to the corresponding imides such as by the procedure described in Rec. Trav. Chim. 69, I490 (1950). As is known in the art, such imides are convertible in high yield to the N-bromotetraalkylsuccinimides which are comparable in utility to such commercial brominating reagents as N- bromosuccinimide [1. Am. Chem. Soc. 85, 3142-6 (1963)]. The 1,4-diketones can also advantageously be employed as intermediates for the preparation of useful compounds including imides as well as diacids and their corresponding esters. For example 3,4-diphenylhexane-2,5-dione (prepared as in example 10) is a useful intermediate for the preparation of 2,3-diphenylsuccinic acid [1. Am. Chem. 500., 70, 1269 (1948)]are known to possess pharmacological utility.

wherein R alkyl of one to 10 carbon atoms, cycloalkyl of from three to eight carbon atoms, alkenyl of from three to 10 carbon atoms, aryl of from six to l0 carbon atoms, heterocyclic of from four to nine carbon atoms, aralkyl of from seven to l 1 carbon atoms,

R alkyl of one to 10 carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of from three to 10 carbon atoms, aryl of six carbon atoms, heterocyclic of four or five carbon atoms, and

considered as a unit is an cycloalkyl radical of three to eight carbon atoms.

2. The process of claim 1 which is carried out at a temperature from about ambient to 200L C.

3. The process of claim 1 wherein manganese dioxide is employed.

4. The process of claim 1 wherein nickel peroxide is employed.

5. A process which comprises treating a ketone having the structure set forth below with manganese dioxide or nickel peroxide to yield a coupling product and recovering the coupling reaction product, the said reactant ketone having the structure wherein R alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of four to six carbon atoms, aryl of six to 10 carbon atoms, heterocyclic of four to nine carbon atoms, aralkyl of eight to 13 carbon atoms, and alkaryl of seven to 11 carbon atoms,

R alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, aryl of six carbon atoms, heterocyclic of four or five carbon atoms and alkaryl of seven carbon atoms, and

considered as a unit is an cycloalkyl radical of three to eight carbon atoms,

R"=alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of two to eight carbon atoms, aryl of six to eight carbon atoms, heterocyclic of four to eight carbon atoms, aralkyl of eight to 14 carbon atoms and alkaryl of seven to l 1 carbon atoms.

6. The process of claim 5 which is carried out at a temperature from ambient to 200L C.

7. The process of claim 5 wherein manganese dioxide is employed.

8. The process of claim 5 wherein nickel peroxide is employed.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 9 193 Dated September 28, 1971 Inventor JOHN CHARLES LEFF INGWELL It is certified that error appears in the above-identified patent, and that said Letters Patent are hereby corrected as shown below:

Column 1, line 3, after "1966" insert now abandoned line 6, "an" should be and line 41, after "atoms," insert and alkaryl of from 7 to 11 carbon atoms,

Column 2, line 36, "Z-methylbutraldehyde" should be 2- methylbutyraldehyde line 41, (J:-methylcyclobutaneacetaldehyde should be amethylcyclobutaneacetaldehyde line 45, "a ,B-dimethylcyclohexane-acetaldehyde" should be a ,3-dimethylcyclohexaneacetaldehyde line 52, "octahydto" should be octahydro line 54, 2-p-ainsyl)-propionaldehyde" should be 2-(p-anisyl)-propionaldehyde,

line 55, "2,Z-di-p-anisyl-acetaldehyde" should be 2,2-di-(panisyl)-acetaldehyde,

line 57, (2'2' furyl)" should be (2'furyl) line 67, "(4'-amlphenyl)" should be (4'- amylphenyl) Column 3, line 10, "p-totyl" should be p-tolyl FORM F'O-1050 {10-69) USCOMM-DC 50376-P59 0 U S GOVERNMENY PRINTING OFFICE I959 O366336 Patent No. 3,609,193

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Dated September 28, 1971 10, "Z-phenyl-l,3-indane-dione" should be 2-phenyl-l,3-indanedione l9, "methycyclopentanone" should be methylcyclopentanone 21, carvementhone (p-methan-Z-one)" should be carvomenthone (p-menthan-Z-one) 28, "Z-methyl-S(p-anisyl)-4-penten-3-one" should be 2-methyl-5-(p-anisyl)-4- penten-3-one "(C4'chlorophen l) should be (4'chlorophenyl "(2'-fruyl)" should be (2'furyl) "Zmethyl-6-phenyl-3un-" should be Z-methyl-6-phenyl-3-u 16, after "dioxide" insert as well as certain commercial manganese dioxide l, "8.75 '1'" (second occurrence) should be 46, "tetramethyl-succinaldehyde" should be tetramethylsuccinaldehyde 8, "cis' and "trans" should be in italics 37, aldehydric" should be aldehydic 39, "trans" and "cis" should be in italics 43, "meso and "d1" should be in italics 53, "d1" and "meso" should be in italics 57, "M--CH 0(M-29) should be M-CH=0 "cis' and trans" should be in italics Patent No. 3,609,193

Dated September 28, 1971 Column 6, line 66, "d1" and "meso" should be in italics Column 7, lines 9 and 10, "cis" and "trans" should be in italics Column 8,

Column 9,

lines 10 and 11, "d1" and "meso" should be in line line

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italics 27, after "components" insert by vapor-phase chromatography. The two major components 46, "aldehyde" should be aldehydic 57, "(CH -CH C)" should be (CH -CH -C-) 61, "3. 69 'r should be 3. 69 p.

"5.80 T" should be 5.80 p

"(-CH -CH should be (-CH -CH "(-Ch CH should be (-C H 2 C H "M-ketone" should be M-kete nz "8.84" should be 7.84

after "(20.1 g.)" delete the "0" "dl and "meso" should be in italics "l86L-" should be 186- "188L" should be 188 "132L-l34L" should be l32-134 "5.87 2" should be 5.87 u

"346/5" should be 346 l 5 "2,2,3,3tetraethylsuccinimide" should be 2,2,3,3-tetraethylsuccinimide Patent No. 3,609,193 Dated September 28, 1971 Column 9, line 38, after "(1948)]" insert the corresponding imide and certain esters of which line 40, before "diethylaminoethyl" insert The Colunm 10, line 3, after "atoms," insert and alkaryl of from 7 to 11 carbon atoms,

line 17, "ZOOLC" should be 200 C.

line 53, "eight" (first occurrence) should be line 57, "20OLC" should be 200 C.

Signed and sealed this 21st day of March 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR. ROBERT GOTTSCIIALK Attesting Officer Commissioner of Patents 

2. The process of claim 1 which is carried out at a temperature from about ambient to 200* C.
 3. The process of claim 1 wherein manganese dioxide is employed.
 4. The process of claim 1 wherein nickel peroxide is employed.
 5. A process which comprises treating a ketone having the structure set forth below with manganese dioxide or nickel peroxide to yield a coupling product and recovering the coupling reaction product, the said reactant ketone having the structure wherein R alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of four to six carbon atoms, aryl of six to 10 carbon atoms, heterocyclic of four to nine carbon atoms, aralkyl of eight to 13 carbon atoms, and alkaryl of seven to 11 carbon atoms, R'' alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, aryl of six carbon atoms, heterocyclic of four or five carbon atoms and alkaryl of seven carbon atoms, and considered as a unit is an cycloalkyl radical of three to eight carbon atoms, R'''' alkyl of one to seven carbon atoms, cycloalkyl of three to six carbon atoms, alkenyl of two to eight carbon atoms, aryl of six to 10 carbon atoms, heterocyclic of four to eight carbon atoms, aralkyl of eight to 14 carbon atoms and alkaryl of seven to 11 carbon atoms.
 6. The process of claim 5 which is carried out at a temperature from ambient to 200* C.
 7. The process of claim 5 wherein manganese dioxide is employed.
 8. The process of claim 5 wherein nickel peroxide is employed. 